This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The use of isotopic labeling with carbon 14 is widespread in biological and medical research, medical diagnostics and drug discovery and development. However, methods to detect radioisotopes depend on the detection of a nuclear decay event, an inefficient process as there is only 1 decay event per minute for every 4.35 billion atoms of 14C present in a sample,requiring the use of high levels of radioactivity. The aim of this project is to demonstrate a device, suitable for routine laboratory use, for atom counting of the tracer 14C, treating 14C as a "stable" isotope, decreasing the dosage required for most experiments and making new classes of studies possible. LARA will be extended from analysis of 13CO2 to similar analysis of 14CO2. Instrumentation will have sensitivity orders of magnitude greater than possible with scintillation (decay) detection and will compete with typical tandem accelerator mass spectrometers (AMS) that have demonstrated sensitivity at the picomole to the attomole level. The enhanced sensitivity is important for low dose and small sample tracer studies, long-term metabolic studies, pharmacokinetics studies and is being studied as a possible tool for protein sequencing and micro-imaging studies. A 14CO2 LARA device is projected to be considerably smaller, less complex and much lower in cost than an AMS with comparable capability. It will be shown that a sealed infrared laser operating at a unique infrared transition in 14CO2, can be routinely used to probe a sample cell containing carbon dioxide. The sample will be in a low pressure electrical discharge optimized for low noise detection of the optogalvanic effect. Such a system can be used to quantitatively measure small samples of 14C-enriched carbon dioxide. Results of the measurements with enriched samples will quantify improvements required to achieve ultimate sensitivity. Techniques will be developed to achieve enhanced sensitivity at the picomole to attomole level. Techniques will include electronic and digital algorithms to lower noise, gas mixture variations to enhance signal and quantum electronic (laser) enhancements. It is further aimed to build prototype instruments for routine laboratory use and transfer the technology to biomedical research facilities. Major progress in the last year led to exceeding design goals and achieving sensitivity of order 10-15 14C/12C ratio with sample size of order 5 to 10 micrograms total carbon . Calibration samples obtained from the Research Resource for Biomedical AMS have been used in these studies.